Research Paper Volume 11, Issue 2 pp 501—522
Prognostic value of immune checkpoint molecules in head and neck cancer: a meta-analysis
- 1 Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China
Received: September 4, 2018 Accepted: January 1, 2019 Published: January 22, 2019
https://doi.org/10.18632/aging.101756How to Cite
Abstract
Immune checkpoint molecules are important targets in cancer immunotherapy, but their association with prognosis in patients with head and neck cancer is controversial. In this meta-analysis, we searched for 12 immune checkpoint molecules in the PubMed, Embase and Cochrane Library databases and retrieved 52 studies with 7127 participants. Among the molecules included in the search, indoleamine 2, 3-dioxygenase (IDO), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) met the inclusion criteria for further analysis. Higher expression of IDO was associated with poorer overall survival in head and neck cancer patients (P = 0.011), but higher expression of PD-L1 correlated with better overall survival specifically in nasopharyngeal carcinoma patients (P = 0.01). In a sensitivity analysis, higher PD-L1 expression correlated with better progression-free survival (P = 0.043), and was associated with better overall survival in Caucasian subjects (P = 0.02), nasopharyngeal carcinoma patients (P = 0.015), and studies with small sample sizes (P = 0.001). PD-1 had no prognostic significance. There was no publication bias affecting the results. Thus, among the immune checkpoint molecules, IDO and PD-L1 are potential prognostic predictors in head and neck cancer.
Abbreviations
PD-L1: programmed death ligand 1; PD-1: programmed death 1; LAG-3: lymphocyte activation gene 3; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; PD-L2: programmed death ligand 2; IDO: indoleamine 2, 3-dioxygenase; VISTA: V-domain Ig suppressor of T cell activation; HR: hazard ratio; M/F: male/female; NA: not available; HNC: head and neck cancer; HNSCC: head and neck squamous cell carcinoma; OSCC: oral squamous cell carcinoma; NPC: nasopharyngeal carcinoma; OPSCC: oropharyngeal squamous cell carcinoma; LSCC: laryngeal squamous cell carcinoma; cut-off value: the value that can be diagnosed as positive/high expression of an immune checkpoint molecule; AQUA: automated quantitative analysis; IHC: immunohistochemistry; IF: immunofluorescence; qRT-PCR: quantitative reverse transcription polymerase chain reaction; FACS: fluorescence-activated cell sorting; FISH: fluorescence in situ hybridization; OS: overall survival; PFS: progression-free survival; DFS: disease-free survival; DSS: disease-specific survival; DMFS: distant metastases-free survival; P: prospective; NOS: Newcastle–Ottawa Quality Assessment Scale; CI: confidence interval.